Implantable medical articles are instrumental in saving patients' lives and enhancing the quality of life for many others. However, a significant barrier to the use of such implantable articles is the possibility of adverse reactions of the body such as thrombogenic and immune responses. Common materials used to manufacture implantable medical articles include metals, minerals or ceramics, and polymers. It is generally desirable to modify the surface of such materials in order to provide the surface with properties that are different from the properties of the material, e.g., in terms of infection resistance, thromboresistance, biodeposition, friction, radiopacity, conductivity and/or biocompatibility. Other desired properties include hydrophilicity, lubricity, ability to mimic natural tissue, and ease of insertion into the body without tissue damage. In addition, it is desirable to have a coating that is durable and abrasion resistant.
Various synthetic techniques have been used to impart desired chemical, physical and biological properties to materials used to manufacture implantable medical articles. One current method of coating medical devices involves application of a parylene coating to devices. For example, parylene C, one of the three primary variants of parylene, can be used to create a moisture barrier on the surface of a medical device. Parylene C is a para-xylylene containing a substituted chlorine atom, which can be coated by delivering it in a vacuum environment at low pressure as a gaseous polymerizable monomer. The monomer condenses and polymerizes on substrates at room temperature, forming a matrix on the surface of the medical device. The coating thickness is controlled by pressure, temperature, and the amount of monomer used. The parylene coating provides an inert, non-reactive barrier.
However, the coating of medical articles with polymers such as parylene C has a number of limitations. For example, parylene C cannot be used to form a thin (e.g., less than 0.1 micron) film with uniform thickness on a medical article. The parylene C application procedure is influenced by the vapor flow through the vacuum chamber, such that areas with different lines of sight, either on a single device or among different devices, receive varying amounts of deposited polymer. Moreover, parylene C requires vacuum conditions to apply the coating, and this requirement complicates the processability of a medical device to be coated using this method. Additionally, the thicker polymer coating, when applied to a metal medical device, such as, for example a stent, will have different physical properties than the underlying metal and, consequently, may not respond similarly to tensile, shear, or compression forces, causing the coating to crack, flake, or delaminate.
Other current methods of coating medical articles typically involve the coupling of compounds directly to surfaces of such articles by ionic or covalent binding. One approach has been to couple biochemical materials, such as heparin or albumin, directly to the surface of the article in order to enhance thromboresistance. For example, albumin has been covalently bound to polymer surfaces in order to improve the biocompatibility of the article by reducing thrombogenicity. See Nicholas A. Peppas et al., "New Challenges in Biomaterials," Science, 263: 1715-1720 (1994).
Medical articles have also been coated with polyurethane or polyethylene terephthalate (PET). See, for example, European Patent Application No. EP 0 769 306 A2, describing a surgical instrument coated with a non-hydrophilic lubricious polymer on the majority of its length located proximally and a hydrophilic polymer located at the majority of the remaining distal length of the instrument. Such coating processes can include, for example, encapsulation of the article with the desired coating. The result of encapsulation is generally a thick layer of polymer surrounding the article. However, the lack of a bond between the polymeric coating and the surface of the article can result in the polymer coating being easily lost.
On a separate subject, silicone-based polymer coatings are currently used to provide controlled modification of surface properties. For example, a siloxane trimonomer film can be used to coat silicone rubber and other materials in order to provide biocompatible coatings with high affinity for albumin. See, for example, Chi-Chun Tsai et al., "Biocompatible Coatings with High Albumin Affinity," ASAIO Transactions, 36: M307-M310 (1990). The siloxane trimonomer is formed by substituting hydroxyl or acyl groups in siloxane side chains, and the resulting siloxane coating preferentially adsorbs albumin from plasma.
Another surface modification technique employing silicone-containing polymers involves direct binding of functional groups to the surfaces of such materials as glass and titanium, using long chains of SiCl.sub.3 terminated amphiphiles. In this method, long-chain alkyltrichlorosilane bearing a remote functionality are bound directly to the material surfaces. The SiCl.sub.3 terminated amphiphiles react with a surface oxide layer (or silanol group on glass), forming a siloxane-anchored network. See, e.g., Sukenik et al., "Modulation of Cell Adhesion by Modification of Titanium Surfaces with Covalently Attached Self-assembled Monolayers," Journal of Biomedical Materials Research, 24: 1307-1323 (1990).
In a broader view, the chemical modification of surfaces to achieve desired chemical and/or physical characteristics has been previously described. See U.S. Pat. Nos. 4,722,906; 4,973,493; 4,979,959; 5,002,582; 5,414,075; and 5,512,329 (each of which are assigned to the present assignee, and the disclosure of each is incorporated herein by reference). These patents generally relate to surface modification by the use of latent reactive groups to achieve covalent coupling of reagents such as biomolecules and synthetic polymers to various substrates. The preferred latent reactive group is typically described as a photochemically reactive functional group (also known as a "photoreactive group") that, when exposed to an appropriate energy source, undergoes a transformation from an inactive state (i.e., ground state) to a reactive intermediate capable of forming a covalent bond with an appropriate material.
Applicants have found that using photoreactive groups to coat polymer layers directly onto a substrate may produce polymer layers that have a tendency to crack when subjected to contortions movement involved in fabricating those substrates into medical devices and/or thereafter, in the course of extended use within the body. This cracking, in turn, may result in the loss of some or all of the coating. The use of thicker coatings does not generally prevent this problem, and in fact can exacerbate this and other problems. What is needed is a way to provide coatings and coating methods for use with such devices, where the coatings exhibit an improved combination of such properties as coating stability, uniformity, and thickness.